SCF-Fbw7 泛素连接酶降解 MED13 和 MED13L，并调节 CDK8 模块与中介体的结合。
The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator.
机构信息
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98117, USA.
出版信息
Genes Dev. 2013 Jan 15;27(2):151-6. doi: 10.1101/gad.207720.112.
Abstract
The Mediator complex is an essential transcription regulator that bridges transcription factors with RNA polymerase II. This interaction is controlled by dynamic interactions between Mediator and the CDK8 module, but the mechanisms governing CDK8 module-Mediator association remain poorly understood. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association. Our work reveals a novel mechanism regulating CDK8 module-Mediator association and suggests an expanded role for Fbw7 in transcriptional control and an unanticipated relationship with the CDK8 oncogene.
摘要
中介复合物是一种重要的转录调控因子，它将转录因子与 RNA 聚合酶 II 连接起来。这种相互作用受中介复合物与 CDK8 模块之间动态相互作用的控制，但调控 CDK8 模块-中介复合物结合的机制仍知之甚少。我们发现，肿瘤抑制因子和泛素连接酶 Fbw7 与 CDK8-中介复合物结合，并靶向 MED13/13L 进行降解。MED13/13L 将 CDK8 模块与中介复合物物理连接，而 Fbw7 的缺失会增加 CDK8 模块-中介复合物的结合。我们的工作揭示了一种调节 CDK8 模块-中介复合物结合的新机制，并表明 Fbw7 在转录调控中具有扩展作用，以及与 CDK8 癌基因的意外关系。
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